The plant cannabinoid Δ 9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

Background and purpose: The phytocannabinoid, Δ 9- tetrahydrocannabivarin (THCV), can block cannabinoid CB 1 receptors. This investigation explored its ability to activate CB 2 receptors, there being evidence that combined CB 2 activation/CB 1 blockade would ameliorate certain disorders. Experimental approach: We tested the ability of THCV to activate CB 2 receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB 2 (hCB 2) receptors; (ii) it stimulated [ 35S]GTPγS binding to hCB 2 CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB 1 or CB 2 receptor antagonist. Key results: THCV inhibited cyclic AMP production by hCB 2 CHO cells (EC 50 = 38 nM), but not by hCB 1 or untransfected CHO cells or by hCB 2 CHO cells pre-incubated with pertussis toxin (100 ng·mL -1) and stimulated [ 35S]GTPγS binding to hCB 2 CHO and mouse spleen membranes. THCV (0.3 or 1 mg·kg -1 i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB 2 receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg·kg -1, and in both phases of this test at 5 mg·kg -1; these effects of THCV appeared to be CB 1 and CB 2 receptor mediated. Conclusions and implications: THCV can activate CB 2 receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB 1 and/or CB 2 receptor activation. © 2010 The British Pharmacological Society All rights reserved.